This invention relates to the administration of a therapeutic gas such as nitric oxide (NO) to patients for therapeutic effect. In particular, it relates to a system wherein a controlled, predetermined dose of NO is provided to the patient with each inhalation by the patient and to the use of various functions utilized by that system to control and/or eliminate nitrogen dioxide (NO2) from the system for safety reasons.
The function of the administration of NO has been fairly widely published and typical articles appeared in The Lancet, Vol. 340, October 1992 at pages 818-820 entitled xe2x80x9cInhaled Nitric Oxide in Persistent Pulmonary Hypertension of the Newbornxe2x80x9d and xe2x80x9cLow-dose Inhalational Nitric Oxide in Persistent Pulmonary Hypertension of the Newbornxe2x80x9d and in Anesthesiology, Vol. 78, pgs. 413-416 (1993), entitled xe2x80x9cInhaled NO-the past, the present and the futurexe2x80x9d.
The actual administration of NO is generally carried out by its introduction into the patient as a gas and commercially available supplies are provided in cylinders under pressure and may be at pressures of about 2000 psi and consist of a predetermined mixture of NO in a carrier gas such as nitrogen. A pressure regulator is therefore used to reduce the pressure of the supply cylinder to working levels for introduction to a patient.
The concentration administered to a patient will vary according to the patient and the need for the therapy but will generally include concentrations at or lower than 150 ppm. There is, of course, a need for that concentration to be precisely metered to the patient since an excess of NO can be harmful to the patient.
One current known method and apparatus for the administration of NO to patients is described in U.S. Pat. No. 5,558,083 where a system is provided that can be added to any ventilator and which will meter in the desired concentration of NO into the gas supplied from that ventilator.
Various other delivery devices have also been used that respond to the patient attempting to inhale to deliver a pulsed dose of NO to the patient and such pulsing devices have also been shown to have therapeutic effect on the patient, for example, as described in Higenbottam PCT patent application WO95/10315 and the publication of Channick et al xe2x80x9cPulsed delivery of inhaled nitric oxide to patients with primary pulmonary hypertensionxe2x80x9d, Chest/109/June 1996. In such pulsatile dosing devices, a pulse of NO is administered to the patient as the patient inhales spontaneously.
The inhalation pulsing type devices are typically shown and described in Durkan, U.S. Pat. No. 4,462,398. Another such apparatus is described in pending U.S. patent application entitled xe2x80x9cConstant Volume NO Pulse Delivery Devicexe2x80x9d, filed on May 16, 1997, U.S. patent application Ser. No. 08/857,924, which was abandoned in favor of U.S. patent application Ser. No. 09/084,710, filed May 26, 1998, now U.S. Pat. No. 6,164,276, issued Dec. 26, 2000.
One difficulty with such devices that provide a supplemental therapeutic gas to the patient concerns the formation of NO2 from NO. NO2 is a toxic compound and its presence is, therefore, undesirable in any appreciable concentration in the gas administered to the patient. Such toxic effects are present at concentrations of about 5 ppm and therefore even minute quantities of NO2 cannot be tolerated.
In the pulse dose devices that administer NO as a supplemental therapeutic gas to the patient, there is likely to be no monitor to sense the presence of NO2 and therefore it is important to take preventative measures in the system itself to assure that the formation of NO2 does not occur, or when it does occur, to remove the NO2 from the system before the NO containing therapy gas is delivered to the patient.
The formation of NO2 results from the reaction of NO with O2 and therefore there is ample opportunity in the administration of NO to a patient for NO2 to be formed. One possibility is when the administration device is connected to the NO therapy gas source, air can be trapped in the cylinder valve and regulator fittings when the connection is made and because the NO in the cylinder is typically only a few hundred parts per million even small volumes of air can provide enough oxygen to cause significant proportions of the NO to react and form NO2. Another possibility is that air can be trapped in passages of the regulator and regulator pressure gauge and which are not in the main flow passages. The main passages are cleared of air during use by the flow of NO therapy gas from the cylinder, however, when the device is turned off for any length of time the O2 in the air can diffuse out of these passages and can react with NO in the regulator and, if the cylinder valve is left open, the O2 can diffuse into the cylinder and react with the NO in the cylinder. The reaction of NO and O2 to form NO2 is a time related reaction, that is, the more time that the NO is in association with the O2, the more NO2 is formed, therefore it is important to provide prevention measures wherever there is any time period where the NO and O2 can be in contact with each other and provide means for removing the NO2 from the system.
Two of the rather critical periods where sufficient time can elapse and where NO and O2 may intermix and where the formation of NO2 may therefore occur are during start-up where NO may have been left in the system in contact with O2 from the prior use of the delivery system and also after a new cylinder has been attached to the delivery device and introduced new quantities of O2 (in air) into the delivery device. Another critical period is the termination of the administration of NO to a patient and the delivery system shut off. At that latter time, unless the cylinder valve controlling the supply of NO containing therapy gas is turned to the off position to isolate the NO supply from the NO delivery system, there is the possibility that any O2 remaining in the conduits of the regulator during the shut down period may migrate back into the cylinder of NO containing therapeutic gas and contaminate that cylinder of gas.
In accordance with the present invention, there is provided a nitric oxide delivery system where a volume of NO is administered to the patient and where certain safety steps are carried out to eliminate NO2 from the system to prevent the inadvertent administration of a toxic concentration of NO2 to the patient.
Therefore, as an aspect of the present invention, at the start up of the system, as indicated, there may be NO2 that formed in the various conduits during the time period when the delivery system was idle. At this point, therefore, the system may, upon the initiation of start-up, provide a visual or audible prompt to the user to carry out the purge manually or, in the alternative, there may be an automatic purge at the initiation of that start-up. In either case, the purge rids the system of any NO2 that may have formed during the time period the system was not in use.
As a further aspect of the present invention, the delivery system detects when the delivery of NO to the patient has been discontinued by the user and the system then either senses the discontinuance of the NO administration and provides a visual and/or audible prompt to the user so that the user can manually shut off the cylinder valve or, alternatively, automatically shuts off the cylinder valve to prevent O2 from migrating back into the cylinder thereby isolating the NO supply from the various conduits and regulator of the NO delivery system. Completion of this step can be confirmed by the system by checking that the flow or pressure in the system goes to zero when a purge is performed after the cylinder valve is turned off. If the valve has not been turned off the pressure or flow during a purge will remain at previous levels and the system can continue the prompt to the user that the cylinder valve needs to be shut off.